Aerosol delivery is important for a number of therapeutic compounds and for treatment of certain diseases. Various techniques for generating aerosols are disclosed in U.S. Pat. Nos. 4,811,731; 4,627,432; 5,743,251; and 5,823,178, each of which is incorporated herein in its entirety.
Local administration of aerosolized drug to treat diseases of the lung include asthma and chronic obstructive pulmonary disease (COPD), lung cancer, and anti-microbial therapy for infectious diseases of the airways. In addition, the lung is increasingly being considered as the portal of entry for a number of aerosolized drugs designed to act systemically. The benefits of administering macromolecular aerosols has been investigated for: insulin, growth hormone, various other peptides and proteins, and gene therapeutic agents.
Aerosol delivery to the airways offers advantages over other routes of administration for several disease states. Direct administration of drug to the lungs has pharmacokinetic and pharmacodynamic advantages, including: greater drug concentration at the intended site of action; reduced systemic side effects; rapid and extensive drug absorption due to the large surface area of the lungs; reduced enzymatic degradation due to the lower metabolic activity of the lung; and avoidance of the first-pass metabolism effect. In addition, drug absorption and dose is not significantly affected by ingested food, patients are familiar with administration techniques, and avoidance of the disadvantages associated with injections.
However, although aerosol delivery to human subjects has been performed routinely for over 50 years, and modified aerosol delivery systems have also been used with animal subjects, delivery systems are still surprisingly inefficient, can be difficult to use, achieve poor targeting, are irreproducible in delivery doses, and are generally inappropriate for newer applications such as gene therapy. Therefore, there remains a long-felt need for novel devices and methods that can produce effective aerosols of therapeutic agents for respiratory delivery to subjects.